Lysosomal storage disorders are caused by a defect in lysosomal function that results in accumulation of substances within the lysosome of cells. This defect is usually a consequence of deficiency of a single enzyme required for the metabolism of lipid, glycogen, glycoprotein, or mucopolysaccharide. Gaucher's disease, the most common lysosomal storage disorder, is characterized by accumulation of the glycolipid glucocerebroside (also known as glucosylceramide), which is caused by a deficiency in β-glucocerebrosidase (also known as beta-glucosidase or GCase).
Many degenerative disorders of the central nervous system are associated with pathologic aggregation of proteins or lipids. For example, synucleinopathies are a group of diseases that arise from disruption of synuclein protein homeostasis. In particular, alpha-synuclein aggregation is associated with pathological conditions characterized by Lewy bodies, such as Parkinson's disease, dementia with Lewy bodies, and multiple system atrophy. Likewise, alpha-synuclein fragment, non-Abeta component, is found in amyloid plaques of Alzheimer's disease. Recently, enhancement of activity in the brain has been shown to prevent accumulation of synuclein in the brain. Thus, agents that enhance GCase activity may provide relief for patients at risk for developing or diagnosed with degenerative disorders of the central nervous system.
Therefore, there is a need for new therapeutic compounds that can be used to prevent and/or treat degenerative disorders of the central nervous system, including synucleinopathies such as Parkinson's disease. There is also a need for new methods to prevent and/or treat lysosomal storage disorders such as Gaucher's disease.
The compound (3R,4R,5S)-5-(difluoromethyl)piperidine-3,4-diol and its hydrochloride salt are first described in U.S. Patent Publication Nos. 2011/0091442 and 2011/0092541, the disclosures of which are incorporated by reference herein in their entireties. The free base form of (3R,4R,5S)-5-(difluoromethyl)piperidine-3,4-diol has the structure according to Formula (I):
and (3R,4R,5S)-5-(difluoromethyl)piperidine-3,4-diol hydrochloride has the structure according to Formula (II):

As described in the '442 and '541 patent application publications, both the compounds of Formula (I) and (II) are potent and selective inhibitors of β-glucocerebrosidase. However, the free base and hydrochloride forms of (3R,4R,5S)-5-(difluoromethyl)piperidine-3,4-diol absorb a high amount of water, which makes it impractical to store these compounds in a high humidity environment. As a result, the free base and hydrochloride forms are not suitable for formulation in dosage forms. Therefore, there is a need for more stable compounds for preventing and/or treating Gaucher's disease and/or Parkinson's disease